What is Hungry Bone Syndrome?

Hypocalcemia is a medical condition where the level of calcium in the blood is too low, which if not found and corrected, may harm your health. One overlooked and often undiagnosed cause of this problem is “hungry bone syndrome” (HBS). HBS usually occurs after surgery such as the removal of the parathyroid or thyroid glands, but it can also occur in patients with certain types of bone cancer. While there is no universally agreed definition of HBS, it is often described as a severe form of low blood calcium, lower than 8.4 mg/dL, that lasts for more than four days after surgery.

What Causes Hungry Bone Syndrome?

Hungry bone syndrome (HBS) is a condition that can happen after certain surgeries, like the removal of the parathyroid glands due to high levels of parathyroid hormone (PTH), or the removal of the thyroid glands due to hyperthyroidism, a condition where the thyroid gland is too active. Parathyroid and thyroid glands are small glands in the neck that regulate certain hormones in the body. It could also occur in cases of advanced prostate cancer that has spread to the bones.

When a person has had a long-term overexposure to PTH or thyrotoxicosis, their bones break down more than usual. But after the surgery, the body quickly switches to rebuilding bone, a process led by cells called osteoblasts. As a result, there’s a high demand for essential minerals used in bone formation, leading to what’s known as HBS.

In males with advanced prostate cancer which has spread to the bones, there can be an increase in osteoblast activity. The extra activity can result in too much bone being made, leading to more minerals being used in bone growth and potentially causing HBS.

Risk Factors and Frequency for Hungry Bone Syndrome

The prevalence of HBS, or Hungry Bone Syndrome, has varied over time and from region to region. Initially, it was estimated that HBS could be found in about 13% of cases after a parathyroidectomy for primary hyperparathyroidism. However, more recent studies report a lower rate of about 4%. Notably, this 4% figure comes from a case study in Saudi Arabia, which is thought to reflect the current expected rate in the U.S., although this can still vary.

In stark contrast, there is data suggesting a much higher rate of HBS in certain Asian populations, possibly up to 87%. It’s thought that this big difference could be down to these populations having better medical care accessibility. With early diagnosis and timely treatment of hyperparathyroidism, the prevalence of HBS can be lessened.

When it comes to cases after a parathyroidectomy for secondary hyperparathyroidism, the prevalence can range from 20% to 70%. Information about the prevalence of HBS in people with tertiary hyperparathyroidism is limited. However, one study found that about 39% of thyrotoxic patients in India had HBS after a thyroidectomy. Additionally, a Singaporean study found that 53% of patients had hypocalcemia (low calcium levels in the blood) that wasn’t caused by post-surgical hypoparathyroidism after a thyroidectomy, but it wasn’t clear whether these were HBS cases.

For HBS in patients with metastatic prostatic cancer, our knowledge is mainly based on individual case reports due to lack of extensive research.

Signs and Symptoms of Hungry Bone Syndrome

Patients with HBS, if they show symptoms, often exhibit signs that are associated with low calcium levels in the body. These symptoms can include seizures, feelings of tightness or contraction in muscles (tetany), unusual skin sensations like prickling or tingling (paresthesias), or a numb or tingling sensation around the mouth or in the hands or feet. Other symptoms might include spasms in the hands or feet (carpopedal spasms), heart rhythm problems (arrhythmias), heart muscle disease (cardiomyopathy), or spasms of the vocal cords that cause difficulty in breathing (laryngospasm).

A physical check-up might reveal a bone fracture or bone deformities, usually resulting from long periods of uncontrolled parathyroid gland activity. There might also be a recent surgical scar from the removal of the parathyroid or thyroid gland. In some cases, there might be signs of excessive nerve activity due to low calcium levels, with specific signs such as Trousseau or Chvostek signs becoming more prominent.

Seizures
Feelings of tightness or contraction in muscles (tetany)
Unusual skin sensations like prickling or tingling (paresthesias)
Numb or tingling sensation around the mouth or in the hands or feet
Spasms in the hands or feet (carpopedal spasms)
Heart rhythm problems (arrhythmias)
Heart muscle disease (cardiomyopathy)
Spasms of the vocal cords causing difficulty in breathing (laryngospasm)
Bone fracture or bone deformities
Recent surgical scar from parathyroid or thyroid gland removal
Signs of excessive nerve activity due to low calcium levels

Testing for Hungry Bone Syndrome

Numerous risk factors have been identified that could increase the likelihood of developing Hungry Bone Syndrome (HBS), a condition characterized by low blood calcium levels after surgery to remove overactive parathyroid glands. Past studies and case reports have pointed to high levels of parathyroid hormone (PTH, a hormone that regulates calcium levels in the body), alkaline phosphatase (an enzyme related to bone and liver health), body mass index (a measure of body fat based on height and weight), blood urea nitrogen (a lab test that assesses kidney function), and the size of the glands that were removed as potential contributing factors. Evidence of bone diseases such as brown tumors, fractures, and osteitis fibrosa cystica (a condition causing bone to become soft and weak), along with an increased number of osteoclasts (cells that break down bone) on a bone biopsy, have also been associated with an increased risk of HBS.

Interestingly, some risk factors appear to be age and condition dependent. For example, older age and high calcium levels before surgery have been identified as risk factors in primary hyperparathyroidism (a condition caused by overactivity of one or more of the parathyroid glands), whereas younger age and lower pre-surgery calcium levels are risk factors in secondary hyperparathyroidism (a condition resulting from diseases of the kidneys).

Unfortunately, it’s been hard to pin down a specific level of PTH that could be used to predict the risk for HBS. The PTH elevation levels in primary hyperparathyroidism are often more subtle, ranging from 300-400 pg/ml, as compared to 700-1000 pg/ml in patients with secondary hyperparathyroidism.

To recap the common risk factors for HBS:

– High levels of PTH
– High levels of alkaline phosphatase
– Evidence of bone disease seen on imaging
– Higher BMI
– Larger parathyroid glands removed
– A higher number of osteoclasts seen on bone biopsy
– High levels of blood urea nitrogen

The risk factors can diverge, based on the specific type of hyperparathyroidism:

– Primary Hyperparathyroidism
– Older age
– High pre-surgery calcium levels
– Secondary Hyperparathyroidism
– Younger age
– Low pre-surgery calcium levels
– Thyrotoxicosis (an overactive thyroid)
– Low bone mineral density in the lower spine

HBS is diagnosed if a person has persistently low calcium levels of less than 8.4 mg/dl for over four days after surgery, with low levels of phosphorus and normal levels of PTH. It may also involve low magnesium levels and low levels of calcium in the urine.

Treatment Options for Hungry Bone Syndrome

If blood tests show that a patient’s calcium level is less than 7.6 mg/dl, if the patient is showing symptoms of low calcium, or if their electrocardiogram (a test that checks how your heart is functioning) shows changes such as an extended QTc interval (a measurement related to the electrical cycles of the heart), these are all signals that treatment with calcium given through an IV (a small tube placed in your vein to deliver medicine) may be needed. There are two different types of calcium that can be administered through an IV: Calcium chloride and Calcium gluconate.

Calcium gluconate is more commonly used, even though calcium chloride contains three times more elemental calcium (the actual amount of calcium in the supplement). This is because calcium gluconate is less irritating if it leaks into the tissue around the IV during treatment. Also, it doesn’t require a special type of IV called a central line to be administered.

The treatment usually starts with a specific dose of calcium gluconate diluted in IV fluids, given over around 5 to 10 minutes. After this initial dose, a continuous stream of calcium gluconate is given through the IV. The calcium level, along with other relevant mineral levels, should be checked every 4 to 6 hours to make sure the treatment is working and the calcium level is getting back to normal.

At the same time as the IV treatment, if the patient is able to take medicines by mouth, they should also start taking calcium supplements orally. The most commonly used oral supplements are calcium citrate and calcium carbonate. Calcium carbonate is often preferred because it provides more calcium and requires fewer pills to take. However, calcium citrate is a better option for people who have reduced stomach acid, such as after certain types of surgery or in older people.

The amount of daily calcium supplement needed can vary greatly among individuals. In cases reported in the past, the amount needed ranged from as low as 800 mg per day to as high as 36 g per day, depending on the specific medical condition and circumstances of the patient.

In addition to calcium, magnesium might also need to be given if the patient’s magnesium level is found to be low. This is because low magnesium can interfere with the actions of a hormone called parathyroid hormone (PTH), which plays an important role in controlling the calcium level.

It’s generally advised to not treat low phosphorus levels as this can cause the phosphorus to combine with calcium and lower the calcium levels even further.

Lastly, while correcting the calcium and possibly magnesium levels, the patient should also start taking activated vitamin D, such as calcitriol. This is because vitamin D is important for the body to properly absorb and use calcium. However, the effects of taking vitamin D will typically not be seen for several days.

Diagnosing why someone’s calcium levels are extremely low, especially after surgery, needs a close inspection of the parathyroid glands. The following situations may contribute to low calcium levels:

Damage to the blood supply of the parathyroid glands during surgery
Accidental removal of all parathyroid glands during surgery
The normal parathyroid glands needing time to recover from making too much parathyroid hormone (PTH) because of a previous overactive gland

Importantly, such conditions might result in low calcium levels, even if PTH levels are below normal and phosphate levels are above normal. This can be a point of contrast to some other conditions where low calcium levels are a symptom.

What to expect with Hungry Bone Syndrome

When it comes to how long HBS (Hungry Bone Syndrome) lasts for patients, there appears to be considerable variation. According to some case studies, patients may need to take calcium and active vitamin D supplements for as long as a year after surgery.

Possible Complications When Diagnosed with Hungry Bone Syndrome

HBS, or Hypoparathyroidism-Bartter syndrome, may lead to major health issues due to the results of hypocalcemia, which is a deficiency of calcium in the bloodstream. In severe cases, this condition can cause seizures, irregular heart rhythms, and heart muscle disease. These conditions can become critical for patients if they’re not identified and treated rapidly.

Preventing Hungry Bone Syndrome

People need to learn about the signs of low calcium levels (hypocalcemia) and the danger of a condition known as hungry bone syndrome. This is particularly crucial for those who have had long-term untreated overactive parathyroid disease (hyperparathyroidism) or thyroid disease (hyperthyroidism). Sometimes, low calcium levels can show no symptoms, so it’s important for them to keep track of their calcium levels after a procedure as part of their overall health care.